Salts of dihydrochalcone derivatives and their use as sweeteners

ABSTRACT

New compounds which are monobasic metal salts of dihydrochalcones and the method of their preparation, the monosodium, monopotassium, and monocalcium salts being useful as sugar substitutes and sweetening agents for foods and beverages.

BACKGROUND OF THE INVENTION

This invention relates to sweetening agents which may be employed assugar substitutes in a wide variety of food, beverage, and confectionaryproducts.

Various dihydrochalcones and their organic derivatives have beenproposed in the prior art as sugar substitutes and sweeteners. In U.S.Pat. No. 3,087,821 there are disclosed various compounds having a highdegree of individual sweetness, such as neohesperidin dihydrochalcone,naringin dihydrochalcone, and prunin dihydrochalcone. These compoundsare prepared by known methods from the corresponding flavanoneglycosides, such as neohesperidin, naringin, prunin and the like, whichoccur naturally in citrus and other fruits, and which may be recoveredas a by-product of the fruit processing operations.

In the preparation of the respective dihydrochalcones, the flavanoneglycosides are dissolved in strong caustic alkalies, such as sodium orpotassium hydroxide solutions, such solutions having concentrations ofthe order of 10% to 25% by weight. The action of the alkali is toconvert the flavanone glycoside to the corresponding chalcone. Thealkali-solubilized flavanone glycoside is then transferred rapidly to anacid environment and subjected to strong acid hydrolysis to avoidseparation of the flavanone glycoside, and to permit formation of thechalcone. Then the chalcone is catalytically reduced with hydrogen toform the dihydrochalcone derivative.

Various processes for the preparation of dihydrochalcone derivativeswhich follow the foregoing basic principles are additionally describedin U.S. Pat. Nos. 2,700,047; 3,375,242; 3,364,196; 3,429,873; and3,522,236. U.S. Pat. NO. 3,429,873 discloses the preparation ofhesperitin dihydrochalcone glucoside, a compound of intense sweetness,from the starting material hesperidin which is itself tasteless. U.S.Pat. No. 3,522,236 describes a propoxy ether of a neohesperidin typedihydrochalcone which also possesses a high level of sweetness.

In all the processes described in the foregoing patents, there isformed, as a result of the initial alkali treatment, a water solublealkali salt of the corresponding chalcone, by reaction of the phenolichydroxyl groups in the flavanone nucleus. When this alkali salt isacidified, the free chalcone is obtained, which is then hydrogenated tothe dihydrochalcone. Thus, at no time is there any formation of analkali salt of the dihydrochalcone product. Moreover, the highconcentration of alkali employed, ranging from 10% to 25%, whichcorresponds to 3 or 4 moles of alkali per mole of flavanone, insuresthat all of the available hydroxyl groups present are neutralized. Theart has recognized, moreover, that the use of less than this molarratio, for example, 2 moles of alkali, was insufficient to form thedesired chalcone. The maintenance of a sufficiently high molar ratio ofalkali to flavanone to effect chalconization is described in U.S. Pat.No. 2,700,047, which indicates that to completely chalconize hesperidin,the requisite ratio of alkali to hesperidin would be about 3 molesalkali to 1 mole hesperidin. However, as pointed out above, no alkalitreatment of the final dihydrochalcone compounds themselves is disclosedor contemplated, nor any salts of those dihydrochalcones which wereknown to be sweet when in their nonionic forms.

GENERAL DESCRIPTION OF THE INVENTION

In accordance with the present invention there are provided novelmonobasic metal salts of dihydrochalcone having the following formula:##SPC1##

wherein R is selected from the group consisting of hydrogen and hydroxy,R' is selected from the group consisting of hydroxy, methoxy, ethoxy andpropoxy, and R" is selected from the group consisting ofneohesperidosyl, β-rutinosyl and β-D-glucosyl, M is a mono- or divalentmetal selected from the group consisting of an alkali metal and analkaline earth metal, and n is an integer from 1 to 2 corresponding tothe valence of the selected metal M.

Typical compounds of the above formula are the alkali or alkaline earthmetal monosalts of the following:

Neokesperidin dihydrochalcone, having the formula: ##SPC2##

2' , 4' , 6' , 3-tetrahydroxy-4-n-propoxydihydrochalcone 4'-βneohesperidoside having the formula: ##SPC3##

naringin dihydrochalcone of the formula: ##SPC4##

prunin dihydrochalcone of the formula: ##SPC5##

hesperidin dihydrochalcone having the formula: ##SPC6##

and hesperitin dihydrochalcone glucoside having the formula: ##SPC7##

In the foregoing general formula the term alkali metal includes sodium,potassium, lithium, rubidium, caesium, and ammonium, while the termalkaline earth metal includes calcium, strontium and barium.

The general method of preparation of the novel monobasic metal salts ofdihydrochalcones, in accordance with the invention, involves thereaction of an alkali metal or alkaline earth metal hydroxide, oxide, orsalt with a mole equivalent of the dihydrochalcone in an aqueous medium,i.e., in a molar ratio of 1 mole of alkali metal compound to 1 mole ofthe dihydrochalcone, or in the case of an alkaline earth metal compound,0.5 mole of alkaline earth metal compound to 1 mole of thedihydrochalcone compound. In the case of alkali metal reactants thehydroxide is preferably employed owing to its ready solubility in theaqueous medium. However, in the case of the more limited solubility ofalkaline earth compounds, the hydroxide, while preferable, may beintroduced in the form of an aqueous suspension. In both cases thedihydrochalcone compound reacts with the base to form a clear aqueoussolution. In the reaction product, in each case, only one of the threefree phenolic hydroxyl groups originally present in the dihydrochalconecompound undergoes salt formation. Where an alkali metal salt is formedthe resulting compound will be a monosodium, monopotassium, and thelike, salt. Where the alkaline earth metal is involved, 2 moles of thedihydrochalcone compound react with the metal, with only 1 of thephenolic hydroxyls in each mole undergoing salt formation.

According to their respective properties, the foregoing salts may finduse in a variety of applications. Thus the lithium compound may be usedindustrially or for specifically medicinal applications. The bariumcompounds may be used, for example, as X-ray contrast media. Theserepresent applications in which taste is of little or no importance.

In accordance with an important aspect of the present invention, it hasbeen found that certain of the monobasic metal salts of the variousdihydrochalcones unexpectedly exhibit improved properties of sweetnessin comparison with the corresponding dihydrochalcones which are known tobe sweet per se in their nonionic forms. The monobasic salt derivativesof the invention are characterized in general by a higher degree ofsolubility and a shorter duration of sweetness than the parentdihydrochalcone compounds. Many of the latter are much lower insolubility than the novel salt derivative sweetners of the invention andpossess a persistence of taste which the salt derivatives do not andwhich in certain applications is undesirable. This opens up new fieldsof use to those monobasic salts derived from non-toxic metals such assodium, potassium, ammonium, and calcium, permitting their use as asubstitute for sugars in the diets of patients having diabetic or otherabnormal metabolic symptons. The monobasic salts of the invention also,in view of their high level of sweetness and short taste persistencecharacteristics, may be used in beverages, soft drinks, confectionery,desserts and the like, particularly for dietetic purposes whennon-persistence and a minimum after taste, coupled with a high degree ofsweetness are sought after qualities. In the case of persons who arerestricted to a low sodium diet, the potassium or calcium derivativesmay be applied.

The sweetening agents of the invention offer a considerably higherdegree of solubility as salts than do the parent compounds from whichthey are derived and possess greater stability both in dry form and insolution than do the parent materials. The salts possess a considerablydifferent taste and duration of taste sensation than the correspondingparent compounds.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following examples serve to illustrate the practice of theinvention, but are not to be regarded as limiting:

EXAMPLE 1 Sodium Salt of Neohesperidin Dihydrochalcone

0.65 gms. of NaOH (0.0163 moles) are dissolved at room temperature in 25ml. H₂ O with stirring. 10 gms. of neohesperidin dihydrochalcone (0.0163moles) is added, which all dissolves. Additional neohesperidindihydrochalcone is added until no more would dissolve. The solution isfiltered and the water removed under vacuum. The resulting solid isyellowish red in color after grinding. The material dissolves readily inwater, being soluble therein in concentration greater than 1 gm/ml., isvery many times sweeter than sucrose, and exhibits markedly differenttaste aspects than the parent material. Decomp. Pt. 172° - 173°C. Theanalysis is:

    ______________________________________                                        Theo.           Actual                                                        ______________________________________                                        C      52.99        53.14    Moisture = 6.26                                  H      5.56         5.54                                                      Na     3.63         3.86                                                      ______________________________________                                    

EXAMPLE 2 Calcium Salt of Neohesperidin Dihydrochalcone

0.605 gms of Ca(OH)₂ (0.0081 mole) is suspended, with stirring, in 50 mlof distilled H₂ O. The slurry is milky in appearance. 10 gms. ofneohesperidin dihydrochalcone (0.0163 moles) is added over a period of10 minutes as a solid. After the first few portions the Ca(OH)₂dissolves and the solution becomes clear and yellow. After 10 gms. isadded 3 additional portions are added until no more neohesperidindihydrochalcone dissolves. The deep green solution is filtered, removingexcess neohesperidin dihydrochalcone and the material is freeze dried.

The product dissolves readily in water having a solubility greater than1 gm/ml. and has markedly different taste aspects than the parentmaterial.

What is claimed is:
 1. As a dietetic sweetner, a monobasic metal salt ofa dihydrochalcone of the formula: ##SPC8##wherein R is selected from thegroup consisting of hydrogen and hydroxy, R' is selected from the groupconsisting of hydroxy and C₁ to C₃ alkoxy, and R" is selected from thegroup consisting of neohesperidosyl, β-rutinosyl, and β-D-glucosyl, M isa mono- or divalent non-toxic metal selected from the group consistingof alkali metals and alkaline earth metals, and n is an integercorresponding to the valence of said selected metal M.
 2. As a dieteticsweetner, the monosodium salt of neohesperidin dihydrochalcone.
 3. As adietetic sweetner, the monocalcium salt of neohesperidindihydrochalcone.
 4. As a dietetic sweetner, a monobasic metal salt of adihydrochalcone of the formula: ##SPC9## wherein R is selected from thegroup consisting of hydrogen and hydroxy, R' is selected from the groupconsisting of hydroxy and methoxy, and R" is selected from the groupconsisting of neohesperidosyl, β-rutinosyl and β-D-glucosyl, n is aninteger from 1 to 2, and M' is selected from the group consisting ofsodium, potassium, ammonium and calcium.